Process and intermediates for the preparation of 3-(amino)-3-cyclobutylmethyl-2-hydroxy-propionamide or salts thereof

Abstract

In one embodiment, the present application relates to a process of making a compound of formula I: and to certain intermediate compounds that are made within the process of making the compound of formula I.

1. A reaction mixture precipitate comprising predominantly the RR and SS enantiomer of Formula VIII; 
       
         
           
           
               
               
           
         
       
       wherein the precipitate is prepared by a process comprising:
 (a) providing a reaction mixture by treating a DMSO solution of the compound of VII, 
 
       
         
           
           
               
               
           
         
       
       with a base in a suitable solvent and subsequently reacting it with peroxide; and
 (b) precipitating the compounds of VIII RR and SS by adding an anti-solvent to the reaction mixture provided by step “a”. 
 
     
     
       2. The precipitate of  claim 1  prepared by the process comprising:
 a) reacting the compound of formula VI with 
 
       
         
           
           
               
               
           
         
       
       to yield a compound of formula VII: 
       
         
           
           
               
               
           
         
         b) hydrating the compound of formula VII in a reaction mixture comprising a low polarity solvent to yield a compound of formula VIII: 
       
       
         
           
           
               
               
           
         
         c) precipitating the RR and SS enantiomer of the compound of Formula VIII by adding water to the reaction mixture from step “b”. 
       
     
     
       3. A reaction mixture precipitate comprising predominantly the RS and SR enantiomer of Formula VIII; 
       
         
           
           
               
               
           
         
         Formula VIII RS Formula VIII SR 
       
       wherein the precipitate is prepared by a process comprising:
 (a) separating the precipitate formed in Step “b” of  claim 1  from the supernatant liquid by filtration; 
 (b) extracting the compounds of Formula VIII RS and VIII SR into ethylacetate; 
 (c) displacing the ethylacetate in the extract formed in Step “b” with n-butylacetate to form a butyl acetate solution comprising predominantly compounds of Formula VIII RS and VIII SR; and 
 (d) precipitating the compounds of compounds of Formula VIII RS and VIII SR from the butyl acetate solution provided in Step “c”.